The failure of functional regeneration in the adult mammalian CNS has been attributed to the lack of an environment which favors axonal elongation and to the loss of growth potential in axons after their original synaptogenesis is completed. The present proposal addresses both of these issues by examining axonal growth after spinal cord lesions in young mammals. The overall purpose of this proposal is 1) to test the ability of fetal spinal cord tissue to promote axonal elongation through the transected spinal cord of neonatal rats, 2) to compare the regenerative capacity of immature axons which are damaged directly by the lesion (rubrospinal tract) with the capacity for growth of immature but later-developing axons (corticospinal tract) which escape direct damage, and 3) to examine the regenerative capacity of the corticospinal tract lesioned at different times in its development, before and after synaptogenesis has taken place. Spinal cord transections will be performed in newborn rats and implants of fetal spinal cord (E12-E14) will be placed within the lesion site. Anterograde and retrograde neuroanatomical tracing techniqus will be used to determine if host axons can elongate into and through the implant. Electron microscopy will be used to examine the interface between host and implant and will be combined with anterograde tracing methods to determine if there are synapses within and caudal to the implant that arise from the host CNS rostral to the lesion. We will compare the growth of the corticospinal tract over substitute terrains to determine if it is simply the mechanical support of the environment that is essential for axonal elongation or if other factors (e.g. trophic and/or tropic support for growing axons) are also important. We will examine the reflex and locomotor function of animals with implants to determine if the anatomical connections mediate recovery of motor function. Double-labeling with retrogradely transported fluorescent dyes will be used to compare the regenerative capacity of axons damaged by the spinal cord lesion with the growth of late-developing axons which escape direct damage, and the regenerative capacity of the corticospinal tract lesioned at different times in its development. We will use quantitative studies of cell survival in the red nucleus to determine if the implants can rescue neurons which die after neonatal axotomy.